Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that plays a critical role in controlling the synthesis and secretion of growth hormone (GH) by the anterior pituitary. Human GHRH is a C-terminal amidated peptide of 44 amino acids. In contrast the rat GHRH is a 43 amino acids long, non-amidated peptide, which is only 67% homologous to human GHRH. It is established that GHRH originates from a precursor (pre-proGHRH) that is processed to mature GHRH by removal of the signal peptide and proteolytic cleavage at C-terminal region. The amino acid sequence of the precursor comprises 107 or 108 residues depending upon differential usage of two possible splice-acceptor sites.
The gene of the human and the rat GHRH includes five small exons separated by 4 introns and spans over 10 kilobases on genomic DNA but differs by the position and the size of the introns.
The patent application EP1052286 illustrates a non-specific method to clone the canine GHRH gene from a genomic library but the description does not disclose the nucleotide sequence of the gene or provides any guidance how to remove the introns and how to assemble the exon sequences to obtain the full coding sequence.
In farm animals, GHRH is galactopoietic with no alteration in milk composition, increases the feed to milk conversion and sustains growth, mostly through increased lean body mass. By stimulation of GH secretion, the GHRH enhances the immune functions in animals. The GHRH have a great therapeutic utility in the treatment of cachexia (Bartlett et al Cancer 1994, 73, 1499-1504 and Surgery 1995, 117, 260-267) in chronic diseases such as cancer, due to growth hormone production abnormalities, in wound healing, bone healing, retardation of the aging process, osteoporosis and in anaemia (Sohmiya et al J. Endocrinol. Invest. 2000, 23, 31-36 and Clin. Endocrinl. 2001, 55, 749-754).
Studies have shown that relatively small amounts of GHRH are required to stimulate the production and the secretion of GH. However the use of a heterologous GHRH, coming from a different animal species, may lead to a less potent stimulation of the release of GH. The therapeutic administration of heterologous GHRH peptide may also induce antibody response in the host. The DNA encoding the canine GHRH was unknown until the present invention and there was a need to make available canine GHRH in sufficient quantity to treat dogs or other animal species.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.